2. Academic Validation
  3. Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition

Anoikis resistance and metastasis of ovarian cancer can be overcome by CDK8/19 mediator kinase inhibition

  • JCI Insight. 2026 Jan 15;11(4):e192113. doi: 10.1172/jci.insight.192113.
Mehri Monavarian 1,  Resha Rajkarnikar 1,  Emily Faith Page 1,  Asha Kumari 1,  Liz Quintero Macias 1,  Felipe Massicano 2,  Nam Y Lee 3,  Sarthak Sahoo 4,  Nadine Hempel 5,  Mohit Kumar Jolly 4,  Lara Ianov 2 6,  Elizabeth Worthey 2,  Abhyudai Singh 7,  Igor B Roninson 8,  Eugenia V Broude 8,  Mengqian Chen 8,  Karthikeyan Mythreye 1
Affiliations

Affiliations

  • 1 Division of Molecular Cellular Pathology, Department of Pathology, O'Neal Cancer Center, Heersink School of Medicine, The University of Alabama, Birmingham, Alabama, USA.
  • 2 UAB Biological Data Science Core, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • 3 Department of Pharmacology, College of Medicine, University of Arizona, Tucson, Arizona, USA.
  • 4 Department of Bioengineering, Indian Institute of Science, Bangalore, India.
  • 5 Division of Malignant Hematology and Medical Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
  • 6 Department of Neurobiology, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • 7 Department of Electrical and Computer Engineering, University of Delaware, Newark, Delaware, USA.
  • 8 Department of Drug Discovery and Biomedical Sciences, College of Pharmacy, University of South Carolina, Columbia, South Carolina, USA.
PMID: 41538289 DOI: 10.1172/jci.insight.192113
Abstract

Anoikis resistance, or evasion of cell death triggered by matrix detachment, is a hallmark of Cancer cell survival and metastasis. We showed that repeated exposure to suspension stress followed by recovery under attached conditions leads to development of anoikis resistance. The acquisition of anoikis resistance was associated with enhanced invasion, chemoresistance, and immune evasion in vitro and distant metastasis in vivo. This acquired anoikis resistance was not genetic, persisting for a finite duration without detachment stress, but was sensitive to CDK8/19 mediator kinase inhibition that could also reverse anoikis resistance. Transcriptomic analysis revealed that CDK8/19 kinase inhibition induces bidirectional transcriptional changes in both sensitive and resistant cells, disrupting the balanced reprogramming required for anoikis adaptation and resistance by reversing some resistance-associated pathways and enhancing Others. Both anoikis resistance and in vivo metastatic growth of ovarian cancers are sensitive to CDK8/19 inhibition, thereby providing a therapeutic opportunity to both prevent and suppress ovarian Cancer metastasis.

Keywords

Apoptosis survival pathways; Cancer; Cell biology; Cell stress; Oncology.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-80013
    99.84%, CDK7 Inhibitor
    CDK